Choroid Plexus Carcinoma in an Adult: Genetic Insights from a Unique Case Study

Choroid Plexus Carcinoma in an Adult: Genetic Insights from a Unique Case Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Choroid Plexus Carcinoma in an Adult: Genetic Insights from a Unique Case Study Wenwu Wan, Fei Chen, Chao Luo, Guang Wang, Xing Peng, Liang Xing, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6108879/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Objective To investigate a rare adult case of choroid plexus carcinoma (CPC), with a focus on identifying genetic variations and their implications for prognosis and treatment selection. Methods The patient was diagnosed with Magnetic Resonance Imaging (MRI) imaging and histopathological features. Next-generation sequencing (NGS) was conducted to identify genetic aberrations. Expression of FGFR2 and FGF19/FGF3/FGF4/CCND1 (11q13 locus genes) identified in our case were further analyzed in two patient cohort from datasets. Statistical analysis assessed correlations between genetic expression and clinical outcomes. Results The amplification of FGFR2 and FGF19/FGF3/FGF4/CCND1, along with TP53 variant (L194P), were identified in our patient. The expression correlation between FGFR2 and 11q13 locus genes was validated in two patient cohorts, CPC and Glioblastoma Multiforme/Low-Grade Glioma (GBM/LGG). FGFR2-11q13 expression effectively stratified patients into distinct survival outcome groups in GBM/LGG cohorts. Discussion The described case contributes to the number of adult patients diagnosed with CPCs and reveals a novel genetic profile. The TP53-FGFR2-11q13 genetic pattern identified in this case holds promise as a prognostic indicator and a guide for medical decision-making in CPCs, and potentially in other brain tumors like GBM/LGG as well. Choroid plexus carcinoma case report FGFR2 11q13 TP53 Figures Figure 1 Figure 2 Figure 3 Introduction Choroid plexus tumors (CPTs), arising from the epithelium of the choroid plexus within the brain ventricles, account for less than 1% of all brain tumors. CPTs encompass choroid plexus papillomas (CPPs), atypical choroid plexus papillomas (aCPPs), and CPCs, and CPCs were the most malignant and invasive subtypes and were categorized as grade III according to the 2021 World Health Organization (WHO) classification. 1 – 2 CPCs occur in only 1–4% of brain tumors in children and are even rarer in adults. 3 While surgical resection remains the cornerstone of treatment, emerging evidence underscores the pivotal role of genetic alterations in influencing CPCs behavior and prognosis. 4 , 5 However, due to limited knowledge of their genetic profile and therapeutic targets, optimal therapy for CPCs has yet to be established. Somatic TP53 mutations have been described in 36–60% of CPCs and are linked to genomic instability and poor prognosis. 5 Nevertheless, other tumor-driving events remain largely unexplored. Here, we present a case of CPC in a 39-year-old female, characterized by intriguing genetic variations, including a TP53 mutation and amplification of FGFR2/11q13 genes, and discuss their potential implications for prognosis and treatment for CPCs and other brain tumors. Methods Genetic analysis NGS detection (OncoDrug-Seq™ pan-cancer) was performed to identify genetic variations across hundreds of genes that are highly associated with tumors, 6 with the sequencing platform being MGISEQ_T7_R1100600200017. The resulting data was aligned with the human reference genome (version hg19) using BWA-MEM software. This NGS test was conducted by Dingjing Biomedical Co., Ltd and the report was generated on January 18, 2024. Datasets The clinical and genetic data for 40 CPTs patients came from GEO (GSE60886), while those for GBM/LGG patients were from TCGA datasets. 7 Statistical Analysis Statistical analyses were conducted using SPSS 26.0 and R software (version 4.1.2), with a significance threshold of P = 0.05. Categorical variables were compared using the Fisher exact test, while continuous variables were assessed using Mann-Whitney U test. Due to the differences in raw data between the two cohorts, the CPT cohort utilized Z-Score to calculate the expression of 11q13 signature genes, whereas the GBM/LGG cohort employed geomean for statistical analysis. 8 The log-rank test was used to compare progression-free survival (PFS) differences between two or more groups in the Kaplan-Meier (KM) survival analysis. Case presentation A 39-year-old female patient from Southwest China, with an unremarkable medical history, presented with a chief complaint of persistent headache and subsequent diplopia in both eyes. In the absence of symptoms like vision loss or vomiting, the examination of extraocular motility revealed bilateral restriction of outward gaze, accompanied by consistent diplopia in all nine cardinal gaze positions. MRI imaging revealed an approximately 25x19 mm irregular nodular lesion within the right lateral ventricle triangle, with homogeneous enhancement on contrast imaging (Fig. 1 ). Surgical intervention was performed to excise the lesion. Histological features of the tumor cells encompassed adenoidal growth patterns, high cellular heterogeneous, prominent nuclear divisions, and Ki-67 proliferation index of 70%, indicative of aggressive proliferation. These findings, in conjunction with specific immunohistochemical markers, led to the definitive diagnosis of CPC, as confirmed by pathologists from two independent hospitals. 9 Post-operative evaluation included positron emission tomography-computed tomography (PET-CT) to exclude metastasis from other primary sites and confirm the absence of residual tumor burden. Furthermore, NGS analysis was performed to evaluate the molecular landscape of the tumor and medical choices. Two months after surgery, the patient underwent whole-brain irradiation as adjuvant treatment. Follow-up MRI scans showed no signs of recurrence or metastasis. The patient remains under close surveillance for any potential recurrence or complications. Results NGS analysis of DNA extracted from the tumor unveiled several intriguing genetic aberrations. A variant of TP53, identified as L194P mutation in exon 6, was discerned. An amplification of FGFR2 (~ 20 fold) was detected, with a concurrent overexpression of FGF19, FGF3, FGF4, and CCND1 genes, all residing in the 11q13 chromosomal locus. 10 It is noteworthy that all of these findings were rare in CPCs. While amplification of the 11q13 locus and FGFR2 has been documented across various malignancies, 11 their roles in CPTs and other brain tumors remain unexplored. Thus, we conducted a detailed expression analysis of FGFR2 and 11q13 genes (FGF19/FGF3/FGF4/CCND1) in a published cohort of patients with CPTs (N = 40). Firstly, we compared expression of FGFR2 and 11q13 genes between benign aCPPs group and malignant CPPs/CPCs group respectively, and there was no difference revealed (Data not shown). An opposite trend was observed between FGFR2 and 11q13 genes in CPCs, particularly pronounced in CPCs harboring TP53 mutation subgroup (r=-0.7, P 0.05). This indicated a potential synergistic role between FGFR2-11q13 deregulation and TP53 mutational status in driving CPT aggressiveness. No such correlation was observed in CPPs or aCPPs, highlighting the specificity of this pattern in CPCs. To further elucidate the FGFR2-11q13 relationship and assess its clinical relevance, we extended our analysis to include the GBM/LGG cohorts from TCGA datasets. Consistently, we observed a contrary expression between FGFR2 and 11q13 genes, irrespective of TP53 status (r=-0.79, P < 0.001) (Fig. 2 B). Clinically, patients within GBM/LGG cohorts who exhibited low expression levels of FGFR2 (FGFR2 low ) demonstrated an inferior prognosis compared to those with high expression of FGFR2 (FGFR2 high ) ( P < 0.05) (Fig. 3 A). Individuals belonging to the 11q13 high group showed a prolonged survival compared to those in the 11q13 low group ( P < 0.001) (Fig. 3 B). Furthermore, patients in the FGFR2 low 11q13 high subgroup showed worse prognosis compared to both FGFR2 low 11q13 low and FGFR2 high 11q13 low subgroups ( P < 0.05), while patients in the FGFR2 high 11q13 low subgroup displayed a survival advantage over both FGFR2 low 11q13 low and FGFR2 high 11q13 high subgroups ( P < 0.05) (Fig. 3 C). In conclusion, our findings underscored an identical contrary relationship between FGFR2 and 11q13 genes in both CPCs and GBM/LGGs, suggesting the potential prognostic value of FGFR2/11q13 expression levels in these brain malignancies. Discussion CPCs are rare and aggressive intracranial neoplasm, posing a diagnostic and therapeutic challenge, particularly in adult patients. In recent years, advances in genomic profiling have shed light on the potential molecular underpinnings and therapeutic targets of CPCs. 5 While TP53 mutations are well-established in pediatric CPCs, genetic alterations in adult cases remain poorly understood. Here, we present a case study of a 39-year-old female patient, accompanied by some genetic variations, marked by a TP53 variant (L194P) and amplifications of the FGFR2 and FGF19/FGF3/FGF4/CCND1. These genetic alterations, which represent novel findings in CPCs, highlight the distinct molecular characterization of this malignancy and emphasize the need for further research to elucidate its underlying mechanisms, develop effective therapeutic strategies and stratify patients for optimized management. TP53, a tumor suppressor gene, stands as one of the most frequently mutated genes across human cancers. In pediatric CPCs, patients harboring low TP53 variation and reduced dysfunction often exhibit a favorable prognosis. 12 In our patient case, a rare TP53 L194P mutation was identified. This mutation has been previously associated with compromised cell growth suppression capabilities, likely contributing to the destabilization of p53 protein function. 13 The specific L194P variant of TP53 was a novel mutation site in the context of both adult and pediatric CPCs. This highlights the potential significance of L194P variant of TP53 in this malignancy, though its precise functional implications still require further elucidation. FGFR2, encoding the fibroblast growth factor receptor and appearing distinct genetic variation in different types of tumor, exhibited a significant (~ 20 fold) amplification in our patient. In human cancers, FGFR2 can be affected by hotspot mutations and structural variants (fusions and amplifications), which have been considered to be oncogenic and actionable due to the resultant overexpression and enhanced receptor stabilization. ATP-competitive small-molecule inhibitors targeting FGFRs have shown promising clinical benefits in patients with cancers harboring such structural variants. 11 Meanwhile, genes encoding fibroblast growth factors (FGFs) and cyclin D1 (CCND1) are co-located in the 11q13 chromosomal region, a hotspot for amplifications in a broad spectrum of human cancers, including breast cancer, ovarian cancer, head and neck cancer, oral cancer, and esophageal cancer. These amplifications contribute to cell proliferation and survival and are associated with poor prognosis and immunotherapy resistance. 14 Notably, in FGFR-aberrant cancers, CCND1 amplifications can confer resistance to FGFRi, therefore FGFRi–CDK4/6i combination therapies have been proposed to enhance response rates in tumors (like breast cancer) with FGFR2 amplifications. 14 – 15 Meanwhile, an analogous oncogenic pattern, including TP53 mutation and amplification of FGFR2, CCND1, and FGFs, have been reported in breast cancers. 11 Given these findings, we postulate that the TP53 (L194P) mutation drives the co-amplification of FGFR2 and CCND1 as well as FGF3/4/19, ultimately contributing to brain tumorigenesis in our patient. This genetic profile inferred a progressive proliferative tumor phenotype, consistent with the high Ki67 index (70%) observed in the tumor cells. Furthermore, the patient may have potential responsiveness to FGFRi-CDK4/6i combination therapy while demonstrating insensitivity to immunotherapy. Considering the frequent occurrence of FGFR2 and 11q13 locus gene amplifications in other solid tumors, we investigated their expression and clinical significance in CPTs and brain tumors. Surprisingly, we found a mutually exclusive expression between FGFR2 and 11q13 genes in CPCs, but not in CPPs or aCPPs, based on analysis of a pediatric patient cohort. Limited by the scarcity of adult cases, we performed further validation in a cohort of common brain tumors (GBM/LGGs). Similarly, an opposite expression trend between FGFR2 and 11q13 signature genes was observed. Unlike other tumor types where FGFR2 amplification is considered oncogenic, we found lower expression of FGFR2 in brain tumors compared to adjacent tissues, correlating with poorer prognosis. Furthermore, GBM & LGG patients with higher expression of 11q13 signature genes showed better prognosis, contrasting with survival outcomes in other tumor types. To assess their prognostic value, we classified patients based on FGFR2 and 11q13 expression levels. In the GBM & LGG patient group, FGFR2-11q13 expression levels effectively stratified patients into distinct survival outcome groups. Since no differences were observed in FGFR2 and 11q13 genes expression between benign and malignant in CPTs, we speculate that the TP53 (L194P) mutation in our patient is more likely to be the driving force of malignancy other than those amplifications. Additionally, the FGFR2-11q13 co-amplification suggests that our case may have a moderate prognosis. The case described herein expands the pool of adult patients diagnosed with malignant CPCs and presents a novel genetic profile for CPC cases. Beyond surgical intervention, medical options and prognostic markers are limited for CPCs, particularly in adult populations. Given the individualized heterogeneity, outcomes vary among patients, prompting research efforts, including the present study, to identify indicators for treatment responsiveness and prognosis prediction. The FGFR2-11q13 expression pattern identified in this case holds promise as a prognostic indicator and a guide for medical decision-making in CPCs, and potentially in other brain tumors like GBM/LGG as well. Nevertheless, it is crucial to note that the underlying interaction mechanisms between FGFR2 and the 11q13 genes in CPCs is still incomplete. Further research is needed to elucidate their roles and interplay. Additionally, it is imperative to identify novel biomarkers and therapeutic targets to enable precise patient stratification and tailored therapeutic approaches for CPC patients. Declarations ·Ethics approval and consent to participate This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Ethics Committee of Chongqing Traditional Chinese Medicine Hospital. Written informed consent was obtained from the patient for participation in this study and collection of medical data. ·Consent for publication Written informed consent for publication of clinical details and any accompanying images was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal. ·Availability of data and materials The original medical imaging data and pathological specimens are archived at Chongqing Traditional Chinese Medicine Hospital in accordance with institutional data retention policies. De-identified clinical data supporting the findings are included in this published article. Due to privacy protection requirements under the consent agreement, complete NGS data are not publicly available but may be available from the corresponding author upon reasonable request. ·Competing interests The authors declare that they have no competing interests relevant to this case report. ·Funding General Program of National Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0628) ·Acknowledgements We thank the clinical team of the Department of Neurosurgery at Chongqing Hospital of Traditional Chinese Medicine for their collaborative care, and particularly acknowledge the patient for consenting to share this educational case. ·Clinical trial number Not applicable Disclosure The authors report no relevant disclosures. Data Availability The datasets generated during the current study are available in the NCBI Sequence Read Archive repository, under BioProject accession number PRJNA1236485 and SRA accession number SRR32704434. References Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231–51. 10.1093/neuonc/noab106 . Sun MZ, Oh MC, Ivan ME, et al. Current management of choroid plexus carcinomas. Neurosurg Rev. 2014;37(2):179–92. 10.1007/s10143-013-0499-1 . Zuo P, Mai Y, Jiang Z, et al. Primary adult choroid plexus carcinomas: a single-center experience with a systematic review. Front Oncol. 2023;13:1260116. 10.3389/fonc.2023.1260116 . Published 2023 Oct 31. Thomas C, Soschinski P, Zwaig M, et al. The genetic landscape of choroid plexus tumors in children and adults. Neuro Oncol. 2021;23(4):650–60. 10.1093/neuonc/noaa267 . Merino DM, Shlien A, Villani A, et al. Molecular characterization of choroid plexus tumors reveals novel clinically relevant subgroups. Clin Cancer Res. 2015;21(1):184–92. 10.1158/1078-0432.CCR-14-1324 . NCCN Biomarkers Compendium. National Comprehensive Cancer Network. Updated 2024. http://www.nccn.org/professionals/biomarkers/content/ URLS. https://portal.gdc.com. Tsoi J, Robert L, Paraiso K, et al. Multi-stage Differentiation Defines Melanoma Subtypes with Differential Vulnerability to Drug-Induced Iron-Dependent Oxidative Stress. Cancer Cell. 2018;33(5):890–e9045. 10.1016/j.ccell.2018.03.017 . Gopal P, Parker JR, Debski R, Parker JC Jr. Choroid plexus carcinoma. Arch Pathol Lab Med. 2008;132(8):1350–4. 10.5858/2008-132-1350-CPC . Dou S, Zhang L, Wang C et al. EGFR Mutation and 11q13 Amplification Are Potential Predictive Biomarkers for Immunotherapy in Head and Neck Squamous Cell Carcinoma. Front Immunol. 2022;13:813732. Published 2022 Mar 16. 10.3389/fimmu.2022.813732 Zingg D, Bhin J, Yemelyanenko J et al. Truncated FGFR2 is a clinically actionable oncogene in multiple cancers [published correction appears in Nature. 2022;609(7929):E13. Nature. 2022;608(7923):609–617. 10.1038/s41586-022-05066-5 Li Y, Liu H, Li T, et al. Choroid Plexus Carcinomas With TP53 Germline Mutations: Management and Outcome. Front Oncol. 2021;11:751784. 10.3389/fonc.2021.751784 . Published 2021 Sep 30. Lu Q, Tan YH, Luo R. Molecular dynamics simulations of p53 DNA-binding domain. J Phys Chem B. 2007;111(39):11538–45. 10.1021/jp0742261 . Kothapalli KSD, Park HG, Kothapalli NSL, Brenna JT. FADS2 function at the major cancer hotspot 11q13 locus alters fatty acid metabolism in cancer. Prog Lipid Res. 2023;92:101242. 10.1016/j.plipres.2023.101242 . Yan K, Zhang D, Chen Y et al. Chromosome 11q13 amplification correlates with poor response and prognosis to PD-1 blockade in unresectable hepatocellular carcinoma. Front Immunol. 2023;14:1116057. Published 2023 Mar 28. 10.3389/fimmu.2023.1116057 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 18 May, 2025 Reviewers agreed at journal 05 May, 2025 Reviews received at journal 27 Apr, 2025 Reviewers agreed at journal 24 Apr, 2025 Reviewers invited by journal 14 Apr, 2025 Editor assigned by journal 09 Apr, 2025 Editor invited by journal 17 Mar, 2025 Submission checks completed at journal 15 Mar, 2025 First submitted to journal 15 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6108879","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":448802668,"identity":"12535d78-e779-48cd-8688-2feeb6700822","order_by":0,"name":"Wenwu Wan","email":"","orcid":"","institution":"Department of Neurosurgery, Chongqing Traditional Chinese Medicine Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wenwu","middleName":"","lastName":"Wan","suffix":""},{"id":448802669,"identity":"399b5d5b-3b17-471f-8ef2-adf48d10c17d","order_by":1,"name":"Fei Chen","email":"","orcid":"","institution":"Department of Neurosurgery, 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01:53:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6108879/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6108879/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82065388,"identity":"33593578-384a-4e7c-8d61-c322ef8f2c87","added_by":"auto","created_at":"2025-05-06 12:29:59","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1223736,"visible":true,"origin":"","legend":"\u003cp\u003eMRI Imaging of the brain.\u003c/p\u003e\n\u003cp\u003eA nodular lesion characterized by long T1 and T2 signal intensities located within the right lateral ventricle triangle. Contrast-enhanced images demonstrated evidently homogeneous enhancement of the lesion, which measured approximately 25*19 mm in size and exhibited irregular morphology.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6108879/v1/43e0cc07f2c9fd32f3886d01.png"},{"id":82065387,"identity":"f8aa2119-b95c-4058-a3aa-35981f538b31","added_by":"auto","created_at":"2025-05-06 12:29:59","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":174086,"visible":true,"origin":"","legend":"\u003cp\u003eThe expression relationship between FGFR2 and 11q13 genes.\u003c/p\u003e\n\u003cp\u003e2A. In CPCs harboring TP53 mutation subgroup, an opposite trend was observed between FGFR2 and 11q13 genes (r=-0.7, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e2B. In GBM/LGG cohorts from TCGA datasets, there was a contrary expression between FGFR2 and 11q13 genes, irrespective of TP53 status (r=-0.79, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001) .\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6108879/v1/194266c6af40f7533b042f54.png"},{"id":82065389,"identity":"64fac68f-4fa7-43bd-b193-3d9d5cb89300","added_by":"auto","created_at":"2025-05-06 12:29:59","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":464531,"visible":true,"origin":"","legend":"\u003cp\u003ePFS according to the FGFR2 and/or 11q13 genes in GBM/LGG cohorts.\u003c/p\u003e\n\u003cp\u003e3A. Patients who exhibited low expression levels of FGFR2 demonstrated an inferior prognosis compared to those with high expression of FGFR2 (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05) .\u003c/p\u003e\n\u003cp\u003e3B. Patiens with high expression of 11q13 genes showed a prolonged PFS compared to those in the low expression group (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001) .\u003c/p\u003e\n\u003cp\u003e3C. Survival Curve for FGFR2/11q13 Subgroups (Left Panel); Corresponding \u003cem\u003eP\u003c/em\u003e-values, HRs, and 95% CIs Between Each Pair of Groups (Right Panel)。\u003c/p\u003e\n\u003cp\u003ePatients in the FGFR2\u003csup\u003elow\u003c/sup\u003e 11q13\u003csup\u003ehigh\u003c/sup\u003e subgroup had shorter PFS compared to both FGFR2\u003csup\u003elow\u003c/sup\u003e 11q13\u003csup\u003elow\u003c/sup\u003e and FGFR2\u003csup\u003ehigh\u003c/sup\u003e 11q13\u003csup\u003elow\u003c/sup\u003e subgroups (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05). Conversely, patients in the FGFR2\u003csup\u003ehigh\u003c/sup\u003e 11q13\u003csup\u003elow\u003c/sup\u003e subgroup displayed a survival advantage over both FGFR2\u003csup\u003elow\u003c/sup\u003e 11q13\u003csup\u003elow\u003c/sup\u003e and FGFR2\u003csup\u003ehigh\u003c/sup\u003e 11q13\u003csup\u003ehigh\u003c/sup\u003e subgroups (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05) .\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6108879/v1/802e967e272eabcab0e0f93b.png"},{"id":82068724,"identity":"9c5290be-5084-4a1b-9ba7-7be7109fb892","added_by":"auto","created_at":"2025-05-06 12:54:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2897308,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6108879/v1/84b5d98a-9c74-4c7e-b1a6-e06cdf9bb9c1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Choroid Plexus Carcinoma in an Adult: Genetic Insights from a Unique Case Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChoroid plexus tumors (CPTs), arising from the epithelium of the choroid plexus within the brain ventricles, account for less than 1% of all brain tumors. CPTs encompass choroid plexus papillomas (CPPs), atypical choroid plexus papillomas (aCPPs), and CPCs, and CPCs were the most malignant and invasive subtypes and were categorized as grade III according to the 2021 World Health Organization (WHO) classification.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCPCs occur in only 1\u0026ndash;4% of brain tumors in children and are even rarer in adults.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e While surgical resection remains the cornerstone of treatment, emerging evidence underscores the pivotal role of genetic alterations in influencing CPCs behavior and prognosis.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e However, due to limited knowledge of their genetic profile and therapeutic targets, optimal therapy for CPCs has yet to be established. Somatic TP53 mutations have been described in 36\u0026ndash;60% of CPCs and are linked to genomic instability and poor prognosis.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Nevertheless, other tumor-driving events remain largely unexplored. Here, we present a case of CPC in a 39-year-old female, characterized by intriguing genetic variations, including a TP53 mutation and amplification of FGFR2/11q13 genes, and discuss their potential implications for prognosis and treatment for CPCs and other brain tumors.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eGenetic analysis\u003c/h2\u003e \u003cp\u003eNGS detection (OncoDrug-Seq\u0026trade; pan-cancer) was performed to identify genetic variations across hundreds of genes that are highly associated with tumors,\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e with the sequencing platform being MGISEQ_T7_R1100600200017. The resulting data was aligned with the human reference genome (version hg19) using BWA-MEM software. This NGS test was conducted by Dingjing Biomedical Co., Ltd and the report was generated on January 18, 2024.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDatasets\u003c/h3\u003e\n\u003cp\u003eThe clinical and genetic data for 40 CPTs patients came from GEO (GSE60886), while those for GBM/LGG patients were from TCGA datasets.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were conducted using SPSS 26.0 and R software (version 4.1.2), with a significance threshold of \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05. Categorical variables were compared using the Fisher exact test, while continuous variables were assessed using Mann-Whitney U test. Due to the differences in raw data between the two cohorts, the CPT cohort utilized Z-Score to calculate the expression of 11q13 signature genes, whereas the GBM/LGG cohort employed geomean for statistical analysis.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e The log-rank test was used to compare progression-free survival (PFS) differences between two or more groups in the Kaplan-Meier (KM) survival analysis.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCase presentation\u003c/h3\u003e\n\u003cp\u003eA 39-year-old female patient from Southwest China, with an unremarkable medical history, presented with a chief complaint of persistent headache and subsequent diplopia in both eyes. In the absence of symptoms like vision loss or vomiting, the examination of extraocular motility revealed bilateral restriction of outward gaze, accompanied by consistent diplopia in all nine cardinal gaze positions. MRI imaging revealed an approximately 25x19 mm irregular nodular lesion within the right lateral ventricle triangle, with homogeneous enhancement on contrast imaging (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Surgical intervention was performed to excise the lesion. Histological features of the tumor cells encompassed adenoidal growth patterns, high cellular heterogeneous, prominent nuclear divisions, and Ki-67 proliferation index of 70%, indicative of aggressive proliferation. These findings, in conjunction with specific immunohistochemical markers, led to the definitive diagnosis of CPC, as confirmed by pathologists from two independent hospitals.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Post-operative evaluation included positron emission tomography-computed tomography (PET-CT) to exclude metastasis from other primary sites and confirm the absence of residual tumor burden. Furthermore, NGS analysis was performed to evaluate the molecular landscape of the tumor and medical choices. Two months after surgery, the patient underwent whole-brain irradiation as adjuvant treatment. Follow-up MRI scans showed no signs of recurrence or metastasis. The patient remains under close surveillance for any potential recurrence or complications.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eNGS analysis of DNA extracted from the tumor unveiled several intriguing genetic aberrations. A variant of TP53, identified as L194P mutation in exon 6, was discerned. An amplification of FGFR2 (~\u0026thinsp;20 fold) was detected, with a concurrent overexpression of FGF19, FGF3, FGF4, and CCND1 genes, all residing in the 11q13 chromosomal locus.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e It is noteworthy that all of these findings were rare in CPCs.\u003c/p\u003e \u003cp\u003eWhile amplification of the 11q13 locus and FGFR2 has been documented across various malignancies,\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e their roles in CPTs and other brain tumors remain unexplored. Thus, we conducted a detailed expression analysis of FGFR2 and 11q13 genes (FGF19/FGF3/FGF4/CCND1) in a published cohort of patients with CPTs (N\u0026thinsp;=\u0026thinsp;40). Firstly, we compared expression of FGFR2 and 11q13 genes between benign aCPPs group and malignant CPPs/CPCs group respectively, and there was no difference revealed (Data not shown). An opposite trend was observed between FGFR2 and 11q13 genes in CPCs, particularly pronounced in CPCs harboring TP53 mutation subgroup (r=-0.7, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA), but not in the TP53 wild type (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). This indicated a potential synergistic role between FGFR2-11q13 deregulation and TP53 mutational status in driving CPT aggressiveness. No such correlation was observed in CPPs or aCPPs, highlighting the specificity of this pattern in CPCs.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTo further elucidate the FGFR2-11q13 relationship and assess its clinical relevance, we extended our analysis to include the GBM/LGG cohorts from TCGA datasets. Consistently, we observed a contrary expression between FGFR2 and 11q13 genes, irrespective of TP53 status (r=-0.79, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Clinically, patients within GBM/LGG cohorts who exhibited low expression levels of FGFR2 (FGFR2\u003csup\u003elow\u003c/sup\u003e) demonstrated an inferior prognosis compared to those with high expression of FGFR2 (FGFR2\u003csup\u003ehigh\u003c/sup\u003e) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). Individuals belonging to the 11q13\u003csup\u003ehigh\u003c/sup\u003e group showed a prolonged survival compared to those in the 11q13\u003csup\u003elow\u003c/sup\u003e group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). Furthermore, patients in the FGFR2\u003csup\u003elow\u003c/sup\u003e 11q13\u003csup\u003ehigh\u003c/sup\u003e subgroup showed worse prognosis compared to both FGFR2\u003csup\u003elow\u003c/sup\u003e 11q13\u003csup\u003elow\u003c/sup\u003e and FGFR2\u003csup\u003ehigh\u003c/sup\u003e 11q13\u003csup\u003elow\u003c/sup\u003e subgroups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), while patients in the FGFR2\u003csup\u003ehigh\u003c/sup\u003e 11q13\u003csup\u003elow\u003c/sup\u003e subgroup displayed a survival advantage over both FGFR2\u003csup\u003elow\u003c/sup\u003e 11q13\u003csup\u003elow\u003c/sup\u003e and FGFR2\u003csup\u003ehigh\u003c/sup\u003e 11q13\u003csup\u003ehigh\u003c/sup\u003e subgroups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). In conclusion, our findings underscored an identical contrary relationship between FGFR2 and 11q13 genes in both CPCs and GBM/LGGs, suggesting the potential prognostic value of FGFR2/11q13 expression levels in these brain malignancies.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCPCs are rare and aggressive intracranial neoplasm, posing a diagnostic and therapeutic challenge, particularly in adult patients. In recent years, advances in genomic profiling have shed light on the potential molecular underpinnings and therapeutic targets of CPCs.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e While TP53 mutations are well-established in pediatric CPCs, genetic alterations in adult cases remain poorly understood. Here, we present a case study of a 39-year-old female patient, accompanied by some genetic variations, marked by a TP53 variant (L194P) and amplifications of the FGFR2 and FGF19/FGF3/FGF4/CCND1. These genetic alterations, which represent novel findings in CPCs, highlight the distinct molecular characterization of this malignancy and emphasize the need for further research to elucidate its underlying mechanisms, develop effective therapeutic strategies and stratify patients for optimized management.\u003c/p\u003e \u003cp\u003eTP53, a tumor suppressor gene, stands as one of the most frequently mutated genes across human cancers. In pediatric CPCs, patients harboring low TP53 variation and reduced dysfunction often exhibit a favorable prognosis.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e In our patient case, a rare TP53 L194P mutation was identified. This mutation has been previously associated with compromised cell growth suppression capabilities, likely contributing to the destabilization of p53 protein function.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e The specific L194P variant of TP53 was a novel mutation site in the context of both adult and pediatric CPCs. This highlights the potential significance of L194P variant of TP53 in this malignancy, though its precise functional implications still require further elucidation.\u003c/p\u003e \u003cp\u003eFGFR2, encoding the fibroblast growth factor receptor and appearing distinct genetic variation in different types of tumor, exhibited a significant (~\u0026thinsp;20 fold) amplification in our patient. In human cancers, FGFR2 can be affected by hotspot mutations and structural variants (fusions and amplifications), which have been considered to be oncogenic and actionable due to the resultant overexpression and enhanced receptor stabilization. ATP-competitive small-molecule inhibitors targeting FGFRs have shown promising clinical benefits in patients with cancers harboring such structural variants.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Meanwhile, genes encoding fibroblast growth factors (FGFs) and cyclin D1 (CCND1) are co-located in the 11q13 chromosomal region, a hotspot for amplifications in a broad spectrum of human cancers, including breast cancer, ovarian cancer, head and neck cancer, oral cancer, and esophageal cancer. These amplifications contribute to cell proliferation and survival and are associated with poor prognosis and immunotherapy resistance.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Notably, in FGFR-aberrant cancers, CCND1 amplifications can confer resistance to FGFRi, therefore FGFRi\u0026ndash;CDK4/6i combination therapies have been proposed to enhance response rates in tumors (like breast cancer) with FGFR2 amplifications.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Meanwhile, an analogous oncogenic pattern, including TP53 mutation and amplification of FGFR2, CCND1, and FGFs, have been reported in breast cancers.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Given these findings, we postulate that the TP53 (L194P) mutation drives the co-amplification of FGFR2 and CCND1 as well as FGF3/4/19, ultimately contributing to brain tumorigenesis in our patient. This genetic profile inferred a progressive proliferative tumor phenotype, consistent with the high Ki67 index (70%) observed in the tumor cells. Furthermore, the patient may have potential responsiveness to FGFRi-CDK4/6i combination therapy while demonstrating insensitivity to immunotherapy.\u003c/p\u003e \u003cp\u003eConsidering the frequent occurrence of FGFR2 and 11q13 locus gene amplifications in other solid tumors, we investigated their expression and clinical significance in CPTs and brain tumors. Surprisingly, we found a mutually exclusive expression between FGFR2 and 11q13 genes in CPCs, but not in CPPs or aCPPs, based on analysis of a pediatric patient cohort. Limited by the scarcity of adult cases, we performed further validation in a cohort of common brain tumors (GBM/LGGs). Similarly, an opposite expression trend between FGFR2 and 11q13 signature genes was observed. Unlike other tumor types where FGFR2 amplification is considered oncogenic, we found lower expression of FGFR2 in brain tumors compared to adjacent tissues, correlating with poorer prognosis. Furthermore, GBM \u0026amp; LGG patients with higher expression of 11q13 signature genes showed better prognosis, contrasting with survival outcomes in other tumor types. To assess their prognostic value, we classified patients based on FGFR2 and 11q13 expression levels. In the GBM \u0026amp; LGG patient group, FGFR2-11q13 expression levels effectively stratified patients into distinct survival outcome groups. Since no differences were observed in FGFR2 and 11q13 genes expression between benign and malignant in CPTs, we speculate that the TP53 (L194P) mutation in our patient is more likely to be the driving force of malignancy other than those amplifications. Additionally, the FGFR2-11q13 co-amplification suggests that our case may have a moderate prognosis.\u003c/p\u003e \u003cp\u003eThe case described herein expands the pool of adult patients diagnosed with malignant CPCs and presents a novel genetic profile for CPC cases. Beyond surgical intervention, medical options and prognostic markers are limited for CPCs, particularly in adult populations. Given the individualized heterogeneity, outcomes vary among patients, prompting research efforts, including the present study, to identify indicators for treatment responsiveness and prognosis prediction. The FGFR2-11q13 expression pattern identified in this case holds promise as a prognostic indicator and a guide for medical decision-making in CPCs, and potentially in other brain tumors like GBM/LGG as well.\u003c/p\u003e \u003cp\u003eNevertheless, it is crucial to note that the underlying interaction mechanisms between FGFR2 and the 11q13 genes in CPCs is still incomplete. Further research is needed to elucidate their roles and interplay. Additionally, it is imperative to identify novel biomarkers and therapeutic targets to enable precise patient stratification and tailored therapeutic approaches for CPC patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e·Ethics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Ethics Committee of Chongqing Traditional Chinese Medicine Hospital. Written informed consent was obtained from the patient for participation in this study and collection of medical data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e·Consent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of clinical details and any accompanying images was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e·Availability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original medical imaging data and pathological specimens are archived at Chongqing Traditional Chinese Medicine Hospital in accordance with institutional data retention policies. De-identified clinical data supporting the findings are included in this published article. Due to privacy protection requirements under the consent agreement, complete NGS data are not publicly available but may be available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e·Competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests relevant to this case report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e·Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGeneral Program of National Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0628)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e·Acknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the clinical team of the Department of Neurosurgery at Chongqing Hospital of Traditional Chinese Medicine for their collaborative care, and particularly acknowledge the patient for consenting to share this educational case.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e·Clinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors report no relevant disclosures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe datasets generated during the current study are available in the NCBI Sequence Read Archive repository, under BioProject accession number PRJNA1236485 and SRA accession number SRR32704434.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLouis DN, Perry A, Wesseling P, et al. 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Front Immunol. 2023;14:1116057. Published 2023 Mar 28. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2023.1116057\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2023.1116057\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Choroid plexus carcinoma, case report, FGFR2, 11q13, TP53","lastPublishedDoi":"10.21203/rs.3.rs-6108879/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6108879/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo investigate a rare adult case of choroid plexus carcinoma (CPC), with a focus on identifying genetic variations and their implications for prognosis and treatment selection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient was diagnosed with Magnetic Resonance Imaging (MRI) imaging and histopathological features. Next-generation sequencing (NGS) was conducted to identify genetic aberrations. Expression of FGFR2 and FGF19/FGF3/FGF4/CCND1 (11q13 locus genes) identified in our case were further analyzed in two patient cohort from datasets. Statistical analysis assessed correlations between genetic expression and clinical outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe amplification of FGFR2 and FGF19/FGF3/FGF4/CCND1, along with TP53 variant (L194P), were identified in our patient. The expression correlation between FGFR2 and 11q13 locus genes was validated in two patient cohorts, CPC and Glioblastoma Multiforme/Low-Grade Glioma (GBM/LGG). FGFR2-11q13 expression effectively stratified patients into distinct survival outcome groups in GBM/LGG cohorts.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe described case contributes to the number of adult patients diagnosed with CPCs and reveals a novel genetic profile. The TP53-FGFR2-11q13 genetic pattern identified in this case holds promise as a prognostic indicator and a guide for medical decision-making in CPCs, and potentially in other brain tumors like GBM/LGG as well.\u003c/p\u003e","manuscriptTitle":"Choroid Plexus Carcinoma in an Adult: Genetic Insights from a Unique Case Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-06 12:29:54","doi":"10.21203/rs.3.rs-6108879/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-05-18T12:48:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"71237474887319715055453393113289440196","date":"2025-05-05T11:15:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-28T03:57:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"16020740384351626598946834444981870928","date":"2025-04-24T21:19:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-14T15:13:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-09T11:50:28+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-03-17T18:54:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-16T02:30:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-03-16T02:29:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3a2caf5e-d4a7-463e-aead-6bb01a14ce26","owner":[],"postedDate":"May 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-05-06T12:29:54+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-06 12:29:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6108879","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6108879","identity":"rs-6108879","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}